This multidisciplinary program focuses on the molecular mechanisms involved in cell survival and on the modalities whereby conventional anti- cancer agents interfere with the function of anti-apoptosis proteins. The program has four projects. There is also request for an administrative and a nucleic acids core component. The investigators intend to study the mechanisms involved in protection from apoptosis by the oncoprotein BCR/ABL and the role of BCR/ABL- dependent anti-apoptotic pathways in leukemogenesis pathways in leukemogenesis, the functional relationship between IGF-1 receptor and BCL-2 family members and the role of this pathway in apoptosis protection, the relevance of post-translational modification of BCL-2 in the anti-tumor effects of certain conventional anti-cancer agents, and the regulation of apoptosis and survival via signals involving novel members of the tumor necrosis factor receptors. The four principal investigators are established and very productive researchers with outstanding track records in the study of cell proliferation, survival, and neoplastic transformation.